Human skin is made up of two main layers, namely the dermis and the epidermis that superficially covers the dermis. Natural human epidermis is composed mainly of three types of cells, namely keratinocytes, which form the vast majority, melanocytes and Langerhans cells. Each of these three types of cells contributes, via its intrinsic functions, to the essential role played in the body by the skin, especially the role of protecting the body against external attacking factors (the climate, ultraviolet rays, tobacco, etc.), which is also known as the “barrier function”.
The epidermis is a keratinized, stratified pavement epithelium 90% made up of keratinocytes. The gradual differentiation of the cells of the basal membrane, which separates the dermis from the epidermis, towards the surface of the epidermis especially includes the differentiation of keratinocytes, which migrate towards the surface of the skin, where they desquamate.
Ageing of the epidermis is manifested mainly by a reduction in its thickness. Atrophy of the epidermis is the consequence of the slowing down of keratinocyte proliferation and of the accumulation of senescent keratinocytes. The horny layer becomes dull.
Desquamation is a natural phenomenon associated with the fact that the epidermis, which constitutes the upper layer of the skin, is in a state of constant regeneration. The epidermis is made up of several layers of cells, the deepest of which is the basal layer formed from undifferentiated cells. Over time, these cells differentiate and migrate towards the surface of the epidermis, constituting the various layers thereof, until they form at the surface of the epidermis the corneocytes, which are dead cells that are removed by desquamation. This surface loss is compensated for by the migration of cells from the basal layer to the surface of the epidermis. This is the phenomenon of perpetual renewal of the skin. Forced removal of the horny layer accelerates the renewal and can combat ageing.
At the same time, these cells continue their differentiation, the final stage of which is the corneocyte. These are in fact dead cells that form the last layer of the epidermis, i.e. the outermost layer also known as the stratum corneum.
Moreover, in the course of chronological and/or actinic ageing, the skin is subjected to oxidative stress, which may be summarized as oxidative attack of all the cellular biological macromolecules (DNA, fats, proteins) by reactive oxygen species (ROS): superoxide radical O2−, hydrogen peroxide H2O2, hydroxyl radical HO°, singlet oxygen 1O2 or nitrogen (RNS: peroxynitrite ONOO, nitrogen monoxide (NO)). This oxidative stress, which may be physiological (for example the consequence of mitochondrial activity) or caused by external agents such as UV, pollution, tobacco, etc., causes cellular impairment (or even cell death) and tissue impairment, which contribute towards ageing of the skin, for instance collagen degradation and thus rigidification of the skin. For the skin, UVA (320-400 nm) are the main sources of cutaneous oxidative stress. They are absorbed by chromophores that transmit the required energy to oxygen to bring it into the reactive singlet state (1O2). UVA also cause the reduction of O2 into superoxide anion (O2∘−), which is itself rapidly dismutated into hydrogen peroxide (H2O2) by the enzyme superoxide dismutase (SOD). H2O2 is then reduced to the hydroxyl radical) (OH°) in the presence of ferrous ion (Fenton reaction) or via the superoxide radical anion (Haber-Weiss). The hydroxyl radical, which is the most reactive, can strip a hydrogen from any surrounding molecule RH, to give the alkyl radical (R°), the precursor form of the peroxyl and alkoxyl radicals (ROO° and RO°) that participate in the propagation phase during an autoxidation. These reactive forms of oxygen are interdependent. It is thus appreciated that it is important to combat cutaneous oxidative stress in order to limit skin ageing.
The dermis provides the epidermis with a solid support. It is also its nourishing element. It is made up mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elastin and a substance known as ground substance. These components are synthesized by the fibroblasts. The cohesion between the epidermis and the dermis is provided by the dermo-epidermal junction. This is a complex region about 100 nm thick, which comprises the basal pole of the basal keratinocytes, the epidermal membrane and the sub-basal zone of the superficial dermis.
Collagens are the major proteins of the extracellular matrices of the skin. To date, 20 types of collagen have been identified, and are noted from I to XX. The collagens predominantly present throughout the epidermis are collagens of the type I and III that form the extracellular matrix of the entire dermis (these collagens constitute 70-80% of the dry weight of the dermis). Moreover, collagens are not all synthesized by the same cell types: collagens of type I and III are essentially produced by the dermal fibroblasts, whereas type VII collagen is produced by two categories of cell, keratinocytes and fibroblasts. Regulation of their expression differs from one collagen to another, for example collagens I and VII are not regulated in the same way by certain cytokines; specifically, TNF-α and leukoregulin stimulate collagen VII and negatively regulate collagen I. Finally, all collagen molecules are variants of a common precursor, which is the α chain of procollagen.
With age, collagen becomes thinner and the fibres become disorganized, and wrinkles appear on the surface of the skin. Cutaneous ageing is partly conditioned by the genetic characteristics.
Moreover, certain environmental factors such as smoking and above all exposure to sunlight accelerate it. The skin thus has a much more aged appearance on the areas exposed to sunlight, such as the back of the hands or the face. Thus, these other factors also have a negative impact on the natural collagen of the skin.
Consequently, given the important role of collagen in the integrity of the skin and in its resistance to external attacking factors of mechanical type, stimulation of the synthesis of these collagens, and in particular of type I collagen, appears to be an effective means for overcoming the signs of ageing of the skin.
During ageing, the skin thus undergoes many modifications and degradations especially in the dermal matrix, which are reflected, with age, by an impairment in the microrelief, flaccid skin, loss of cutaneous suppleness, the appearance of wrinkles and fine lines, the appearance of pigmentation marks, loss of radiance of the complexion and also an impairment in the mechanical properties of the skin, especially lack of elasticity of the skin.
The importance of having available products whose effects are directed towards combating the overall signs of ageing, regenerating skin tissue via increasing keratinocyte proliferation and stimulating fibroblast proliferation and/or metabolism, and especially stimulating collagen synthesis, may thus be appreciated.